Millennium Challenge Series #31- Challenges of Managing Resistant Strains of Infectious Diseases- Lessons of Gonocci resileance

Dear Patriotic Ethiopians and Friends of Ethiopia:

Re: Millennium Challenges Series #31: Health Alets for Millennium travelors: Managing drug resistance of common infectious diseases- Lesson from US Gonococci Resilience!Is HIV Therapy different?

Micro-organisms are considered the living witness of "evolution inn progress" as they are able to mutate and change their genetic markers and survival skills within shorter periods than any other living organisns and some consider them as the bio-tracers of Evolution in progress. Some even take them as the living proof for the controversial Evolution Versus Creation theories and their impact on our educational and social dynamics of the 8th Millennium.

Most infectious diseases or micro-organisms florish in the Tropical Belt across the world where Africa has the largest land mass and people sharing the most conducive ecology for micro-organisms and infectious disease with plants, animals and humans.

As such Infectious Diseases (viruses, bacteria and parasites, etc) continue to be the main immunological challenge of our health system, where modern research is showing that almost all the current set of disabling chronic conditions such cardio-vascular, neurological and degenerative disease share the same pathway of "our bodies' response to inflamation that generates hypersensitivity and gradual damage to our immmune system and respective target organs.

The viruses are known for their efficiency in their ability to mutate and the bacterias are not behind in this exceptional skill of survival of the fitest in the most hostile pharmacological environment modern medicine has placed them.

As the rna virus cuase of the pandemic HIV/AIDS challenge is mutating in a highly efficient manner overtaking the drug production, distribution and administration skills of our modern medical system, Niesseria gonococcus, the cuase of one of the most common sexually transmitted diseases are not left behind.

The attached CDC Guidelines from the US explains this rather interesting story which I believe is an important development for people in public health and public policy arena.

It is critical to take note, that prevention and early intervention focussed on "pre-test and post test counseling" and appropriate early intervention supported by aggressive and efficient "contact tracing of all sexual contacts of at-risk population" is the most effective and cost efficient way of treating infectious diseases.

As people are planning to visit Ethiopia around September 2007, the Ethiopian Health Authorities and medical centers should be aware of this new development of resistant strains of gonococci and make the appropriate transition from Penicillin, Tetracyclines and Fluoroquinones (ciprofloxacin, Ofloxium etc, to the preferred drug of Cehalosporins, etc.

Please read for further details in the attached article. However, the most potent means of addressing "Drug Resistance and potential potent viruses and bacterias is to resport the most effective means of prevention and early intervention strategy mentioned above.


Yours sincerely

Belai Habte-Jesus, MD, MPH
Global Strategic Enterprises, Inc
Partners for Peace and Prosperity
www.Globalbelai4u.blogspot.com
globalbelai@hotmail.com


CDC Issues New Treatment Recommendations for Gonorrhea CME/CE
News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD
Disclosures

Release Date: April 16, 2007; Valid for credit through April 16, 2008 Credits Available

Physicians - maximum of 0.5 AMA PRA Category 1 Credit(s)™ for physicians;
Family Physicians - up to 0.5 AAFP Prescribed credit(s) for physicians;
Nurses - 0.5 nursing contact hours (0.5 contact hours are in the area of pharmacology)



April 16, 2007 — The US Centers for Disease Control and Prevention (CDC) have issued new treatment recommendations for gonorrhea, which are published in the April 13 issue of the Morbidity and Mortality Weekly Report. The new guidelines recommending cephalosporin treatment are in response to gonorrhea resistance to fluoroquinolones, which is now widespread in the United States among heterosexuals and men who have sex with men.

"Gonorrhea is the second most commonly reported infectious disease in the US, with about 340,000 cases reported in 2005," John M. Douglas, Jr., MD, Director of the Division of Sexually Transmitted Diseases Prevention (DSTD), National Center for HIV/AIDS, Viral Hepatitis, STD [sexually transmitted disease], and TB Prevention (NCHHSTP), said in a CDC teleconference. "Like most STDs, gonorrhea is underdiagnosed and underreported, and we estimate that about twice that number of people were affected. We've made substantial progress in reducing the burden of gonorrhea over the years as a result of efforts to prevent, detect and effectively treat the disease."

Rising rates of gonorrhea resistance to fluoroquinolones were first noted in Hawaii and California, leading the CDC to recommend in 2000 and in 2002, respectively, that fluoroquinolones not be used to treat gonorrhea infections in these states. In 2004, rising rates of gonorrhea resistance to fluoroquinolones in men who have sex with men led the CDC to recommend against using fluoroquinolones in this group.

"Part of our success in controlling this disease has been our ability to treat the changing organism itself," Dr. Douglas says. "Gonorrhea has proven to be quite efficient at navigating around the drugs we use to combat it, with resistance first to penicillin, then tetracycline, then, most recently, to fluoroquinolones.... We want a recommended treatment to cure 95% or more of all gonorrhea infections, [and] we have reached a level of resistance that threatens our ability to control the disease across populations."

Data from CDC's Gonococcal Isolate Surveillance Project (GISP) in 26 US cities showed that in the first half of 2006, 6.7% of gonorrhea cases in heterosexual men were fluoroquinolone-resistant Neisseria gonorrhoeae (QRNG), an 11-fold increase from 0.6% in 2001, and well above 5%, the recognized threshold for changing treatment recommendations.

"As a result of these increases in fluoroquinolone resistance throughout the country, CDC is no longer recommending that fluoroquinolones be used to treat gonorrhea anywhere in the U.S.," Dr. Douglas says. "These recommendations are critical to preserve the progress we've made in controlling gonorrhea, one of the nation's most common STDs."

The overall proportion of gonorrhea cases that were QRNG increased from less than 1% in 2001 to 13.3% in the first half of 2006, with dramatic increases from 2004 to 2006 in Philadelphia (1.2% - 26.6%) and Miami (2.1% - 15.3%). QRNG also continued to rise among men who have sex with men, from 1.6% in 2001 to 38% in the first half of 2006.

"We do not have the full data yet from the last half of 2006," Hillard S. Weinstock, MD, MPH, Medical Epidemiologist, DSTD, NCHHSTP, said in the teleconference. "However, given the trends we have observed over the last several years, we expect that the percentage of fluoroquinolone-resistant cases will go up in the second half of 2006."

Therefore, the CDC no longer recommends fluoroquinolone antibiotics (ciprofloxacin, ofloxacin, and levofloxacin) for treatment of gonorrhea in the United States. Because gonorrhea resistance to penicillin, sulfa drugs, and tetracycline is already widespread, this limits available options for gonorrhea treatment to drugs in the cephalosporin class. The United Kingdom preceded the United States by about 3 to 4 years in its recommendation to switch from fluoroquinolones to cephalosporins in gonorrhea treatment.

"There is an urgent need for new, effective medicines to treat gonorrhea," Kevin Fenton, MD, Director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said in a news release. "We are running out of options to treat this serious disease. Increased vigilance in monitoring for resistance to all available drugs is essential."

Although significant resistance to cephalosporins has not been reported thus far, CDC is collaborating with state and local health departments to detect emerging cephalosporin resistance. Now that gonorrhea is largely diagnosed by a convenient DNA test, many laboratories and providers no longer have the capability of culturing N gonorrhoeae for drug resistance testing. The CDC is urging health departments to maintain or develop this capacity and to evaluate any gonorrhea treatment failures for possible resistance.

"Importantly, with fluoroquinolones no longer recommended, only one class of drugs remains recommended for treating gonorrhea: the antibiotics known as cephalosporins," Dr. Douglas says. "Although the cephalosporins offer several potential options for treating gonorrhea, the lack of additional classes of antibiotics is a serious concern. There are currently no new drugs for gonorrhea in the drug development pipeline."

To bolster international monitoring for the emergence of cephalosporin resistance, CDC is also working with the World Health Organization (WHO) and with government and industry partners to identify and evaluate new drug regimens for gonorrhea treatment.

"While we have not seen any evidence of resistance to cephalosporins to date, emergence of any resistance would be a serious public health concern," Dr. Douglas said. "CDC will work with government and industry partners to identify and evaluate promising alternative drug regimens for treating gonorrhea. Ultimately, reducing the burden of gonorrhea will require comprehensive and continued action on many fronts, as we work to maintain and expand effective programs to prevent and control this disease across the nation."

Most cases of gonorrhea in women are asymptomatic and untreated. However, failure to treat gonorrhea aggressively and early may result in pelvic inflammatory disease with associated infertility, chronic pelvic pain, and/or ectopic pregnancy. In men, rare complications of untreated gonorrhea may include epididymitis, rarely associated with infertility.

Even when asymptomatic, inflammation of the male genitourinary tract associated with gonorrhea may increase susceptibility to HIV infection. Rarely, untreated gonorrhea may be associated with serious sequelae such as infectious arthritis, meningitis or endocarditis.

Updated recommended treatment regimens for gonorrhea infection are as follows:

For uncomplicated gonococcal infections of the cervix, urethra, and rectum, recommended treatments are 125 mg of ceftriaxone in a single intramuscular (IM) dose or 400 mg of cefixime (not available in the United States) in a single oral dose, plus treatment of Chlamydia if chlamydial infection is not ruled out. Although 400-mg tablets of cefixime are not available in the United States, and it is only available in a suspension formulation, Dr. Douglas said that the CDC has approached the Food and Drug Administration regarding this, and they are hopeful that oral tablets will soon be an option in the United States.

"While we only have this single class of recommended antibiotics, the cephalosporins, and the vigilance we've talked about today is a key public health priority, we've been using this class of drugs for the treatment of gonorrhea since the early 1980s, and fortunately, so far, there has not been any documentation of emergence of resistance," Dr. Douglas says. "I don't want to present an injectable antibiotic as an insurmountable obstacle, because we used it for years with penicillin; it's more of a bump in the road in terms of how providers will be caring for patients with gonorrhea."

Alternative regimens for uncomplicated gonococcal infections of the cervix, urethra, and rectum are 2 g of spectinomycin (not available in the United States) in a single IM dose or cephalosporin single-dose regimens (ceftizoxime, 500 mg IM; or cefoxitin, 2 g IM, administered with probenecid, 1 g orally; or cefotaxime, 500 mg IM).

For uncomplicated gonococcal infections of the pharynx, recommended regimens are 125 mg of ceftriaxone in a single IM dose, plus treatment of Chlamydia if chlamydial infection is not ruled out. There are currently no recommended alternatives for pharyngeal infection.

For disseminated gonococcal infection, pelvic inflammatory disease, epididymitis, and treatment of gonorrheal infections in patients with documented severe allergic reactions to penicillins or cephalosporins, updated treatment regimens are available at http://www.cdc.gov/std/treatment.

A limitation of findings from GISP, which is conducted in publicly funded clinics and includes only male urethral isolates, is that they might not be representative of the entire US population infected with gonorrhea.

"We've looking hard for resistance for the duration of the GISP project, and we've never seen gonorrhea that we would consider to be resistant to cephalosporins," Dr. Douglas said. "Based on global surveillance, we have not documented any strains resistant to cephalosporins at all. That's comforting, of course, but because of the genetic versatility of the organism, it's not something we feel completely complacent about.

Although test of cure is not recommended routinely for uncomplicated gonorrhea treated with recommended or alternative regimens, persons with persistent symptoms of gonococcal infection or whose symptoms recur shortly after treatment with a recommended or alternative regimen should be reevaluated by culture for N gonorrhoeae. Positive isolates should be tested for antimicrobial susceptibility, and clinicians and laboratories should report treatment failures or resistant gonococcal isolates to the CDC at the telephone number: 1-404-639-8373, through state and local public health authorities.

"In [other] Gram-negative bacteria, very highly resistant strains even to these third generation cephalosporin antibiotics have occurred," Dr. Douglas concluded. "It's just very hard to know if that could happen [for N gonorrheae], and when it could happen, but it's certainly not implausible. Can it happen? Absolutely."

Morbid Mortal Wkly Rep. 2007;56:332-336.

http://www.cdc.gov/std/treatment

http://www.cdc.gov/std/gonorrhea/arg/

Clinical Context

In the United States, gonorrhea is the second most frequently reported notifiable disease, with 339,593 cases documented in 2005. Although fluoroquinolones (ciprofloxacin, ofloxacin, or levofloxacin) are highly effective, readily available, and convenient as single-dose oral therapy and have been used since 1993 for gonorrhea treatment, prevalence of fluoroquinolone resistance in N gonorrhoeae has been increasing and is now widespread.

Beginning in 2000, fluoroquinolones were no longer recommended for treatment of gonorrhea acquired in Asia or the Pacific Islands (including Hawaii); in 2002, this recommendation was extended to California; and in 2004, CDC recommended that fluoroquinolones not be used in the United States to treat gonorrhea in men who have sex with men. This Morbidity and Mortality Weekly Report article summarizes findings from the GISP and updates CDC's Sexually Transmitted Diseases Treatment Guidelines, 2006 regarding the treatment of N gonorrhoeae infections.

Study Highlights

GISP data from 26 US cities showed that in the first half of 2006, 6.7% of gonorrhea cases in heterosexual men were QRNG. This represents an 11-fold increase from 0.6% in 2001 and exceeds 5%, the recognized threshold for changing treatment recommendations.

In the first half of 2006, the overall proportion of gonorrhea cases that were QRNG increased to 13.3%, up from less than 1% in 2001, and QRNG among men who have sex with men rose from 1.6% in 2001 to 38%. From 2004 to 2006, QRNG increased sharply in Philadelphia (1.2% - 26.6%) and Miami (2.1% - 15.3%).
Therefore, the CDC no longer recommends fluoroquinolone antibiotics (ciprofloxacin, ofloxacin, and levofloxacin) for treatment of gonorrhea in the United States. Because gonorrhea resistance to penicillin, sulfa drugs, and tetracycline is already widespread, this limits available options for gonorrhea treatment to drugs in the cephalosporin class.

Resistance to cephalosporins has not been reported to date. To detect emerging cephalosporin resistance, CDC is collaborating with state and local health departments. Now that gonorrhea is largely diagnosed by a convenient DNA test, many laboratories and providers no longer have the capability of culturing N gonorroheae for drug resistance testing. The CDC is urging health departments to maintain or develop this capacity and to evaluate any gonorrhea treatment failures for possible resistance.

To improve international monitoring for the emergence of cephalosporin resistance, CDC is also working with the WHO and with government and industry partners to identify and evaluate new drug regimens for gonorrhea treatment.

Most cases of gonorrhea in women are asymptomatic and untreated, but complications. may include pelvic inflammatory disease with associated infertility, chronic pelvic pain, and/or ectopic pregnancy. In men, rare complications of untreated gonorrhea may include epididymitis, and rarely infertility. Inflammation of the male genitourinary tract linked with gonorrhea may increase susceptibility to HIV infection. Rarely, untreated gonorrhea may be linked with serious sequelae such as infectious arthritis, meningitis, or endocarditis.

Updated recommended treatment regimens for uncomplicated gonococcal infections of the cervix, urethra, and rectum are 125 mg of ceftriaxone in 1 IM dose or 400 mg of cefixime (not available in the United States) in 1 oral dose, plus treatment of Chlamydia if this infection is not ruled out.
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Alternative regimens for uncomplicated gonococcal infections of the cervix, urethra, and rectum are 2 g of spectinomycin (not available in the United States) in 1 IM dose, or cephalosporin single-dose regimens (ceftizoxime, 500 mg IM; or cefoxitin, 2 g IM, administered with probenecid, 1 g orally; or cefotaxime, 500 mg IM).
For uncomplicated gonococcal infections of the pharynx, recommended regimens are ceftriaxone, 125 mg in a single IM dose, plus treatment of Chlamydia if not ruled out. There are presently no recommended alternatives for pharyngeal infection.
Updated treatment regimens are available from CDC for disseminated gonococcal infection, pelvic inflammatory disease, epididymitis, and treatment of gonorrheal infections in patients with documented severe allergic reactions to penicillins or cephalosporins.

Test of cure is not recommended routinely for uncomplicated gonorrhea treated with the above regimens. Persons with persistent or recurrent symptoms after treatment should be cultured for N gonorrhoeae. Positive isolates should be tested for antimicrobial susceptibility, and treatment failures or resistant isolates should be reported to the CDC.

Pearls for Practice
CDC data from GISP in 26 US cities showed that in the first half of 2006, 6.7% of gonorrhea cases in heterosexual men were QRNG. In the first half of 2006, the overall proportion of gonorrhea cases that were QRNG increased to 13.3%, up from less than 1% in 2001, and QRNG among men who have sex with men rose from 1.6% in 2001 to 38%.

Fluoroquinolones are therefore no longer recommended for gonorrhea treatment anywhere in the United States, either in heterosexuals or in men who have sex with men. Cephalosporins are the only remaining drug class to which N gonorrhoeae has not demonstrated resistance. Updated recommended treatment regimens for uncomplicated gonococcal infections of the cervix, urethra, and rectum are 125 mg of ceftriaxone in 1 IM dose or 400 mg of cefixime (not available in the United States) in 1 oral dose, plus treatment of Chlamydia if this infection is not ruled out.